US3887577A - Process for the preparation of 2-imino derivatives of substituted imidazoles - Google Patents
Process for the preparation of 2-imino derivatives of substituted imidazoles Download PDFInfo
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- US3887577A US3887577A US376493A US37649373A US3887577A US 3887577 A US3887577 A US 3887577A US 376493 A US376493 A US 376493A US 37649373 A US37649373 A US 37649373A US 3887577 A US3887577 A US 3887577A
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- Prior art keywords
- imidazolin
- methyl
- phosphorus oxychloride
- preparation
- lower alkyl
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- 238000000034 method Methods 0.000 title claims description 34
- 150000002460 imidazoles Chemical class 0.000 title abstract description 7
- 238000002360 preparation method Methods 0.000 title description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims abstract description 36
- AICIYIDUYNFPRY-UHFFFAOYSA-N 1,3-dihydro-2H-imidazol-2-one Chemical compound O=C1NC=CN1 AICIYIDUYNFPRY-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 24
- 238000010992 reflux Methods 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 12
- 150000003141 primary amines Chemical class 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 8
- FAXDZWQIWUSWJH-UHFFFAOYSA-N 3-methoxypropan-1-amine Chemical group COCCCN FAXDZWQIWUSWJH-UHFFFAOYSA-N 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 3
- KLHDTEQBZYFFKQ-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-4-methyl-1-propan-2-ylimidazol-2-one Chemical group O=C1N(C(C)C)C=C(C)N1C1=CC=C(Cl)C(Cl)=C1 KLHDTEQBZYFFKQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 2
- KSCWCQMTKWRPKT-UHFFFAOYSA-N 4-methyl-3-phenyl-1-propan-2-ylimidazolidin-2-one Chemical group CC1N(C(N(C1)C(C)C)=O)C1=CC=CC=C1 KSCWCQMTKWRPKT-UHFFFAOYSA-N 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- SBHLGVQLCSTTQF-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-n,4-dimethyl-1-propan-2-ylimidazol-2-imine Chemical compound CN=C1N(C(C)C)C=C(C)N1C1=CC=C(Cl)C(Cl)=C1 SBHLGVQLCSTTQF-UHFFFAOYSA-N 0.000 abstract 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 125000000217 alkyl group Chemical group 0.000 description 17
- 239000000047 product Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- -1 methoxy, ethoxy, propoxy, isopropoxy, butoxy Chemical group 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 3
- 238000010183 spectrum analysis Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical class O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 1
- 229940120124 dichloroacetate Drugs 0.000 description 1
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000026267 regulation of growth Effects 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
Definitions
- the hydrochloride salt is dissolved in 1000 ml water and extracted with 3 250 ml of diethyl ether.
- the aqueous layer is made basic by the addition of 1500 g of cold 25% sodium hydroxide solution and then extracted with 5X200 ml of diethyl ether, dried over magnesium sulfate and subjected to high vacuum to remove any residual methoxypropyl amine.
- Approximately 204.7g of the free base is obtained which is dissolved in 200 ml of acetone and a solution of 94 g of oxalic acid dihydrate in about 300 ml of acetone is added.
- the solution is diluted with an equal volume of ethyl acetate and cooled to provide 181 g. of product.
- the mother liquor is evaporated and the residue recrystallized from isopropanol to give an additional 11.6 g of product for total yield of 192.6 g NMR spectral analysis of the product confirmed the following structure.
- R is lower alkyl or lower alkoxy lower alkyl, R is lower alkyl; R is lower alkyl or hydrogen; R is lower alkyl or hydrogen; Z is fluoro, chloro, bromo, lower alkyl, halo lower alkyl, or lower alkoxy and n is an integer zero through 2, which comprises reacting at temperatures from about 40C. up to the reflux temperature of the system a 4-imidazolin-2-one of the formula wherein R, R R", Z and n are as defined above, with phosphorus oxychloride and a primary amine of the formula H NR wherein R is as defined above.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A class of 2-imino derivatives of substituted imidazoles are prepared by the reaction of a 4-imidazolin-2-one with phosphorus oxychloride and a primary amine. Representative of this class is 1-isopropyl-2-methylimino-3-(3,4-dichlorophenyl)-4-methyl-4imidazoline.
Description
United States Patent [1 1 Dixon June 3,1975
[ PROCESS FOR THE PREPARATION OF 2-IMINO DERIVATIVES OF SUBSTITUTED IMIDAZOLES [75] Inventor: v William D. Dixon, Kirkwood, Mo. [73] Assignee: Monsanto Company, St. Louis, Mo.
[22] Filed: July 5, 1973 [21] Appl. No.: 376,493
[52] U.S. Cl 260/309.6; 71/92 [51] Int. Cl C07d 49/36 [58] Field of Search 260/3096 [56] References Cited OTHER PUBLICATIONS Burmistrov et al., C. A., Vol. 62: 14657, (1965).
Primary Examiner-I-Ienry R. .Iiles Assistant ExaminerC. M. S. Jaisle Attorney, Agent, or Firm-William I. Andress; Donald W. Peterson; Neal E. Willis [5 7] ABSTRACT 11 Claims, No Drawings PROCESS FOR THE PREPARATION OF 2-IMINO DERIVATIVES OF SUBSTITUTED IMIDAZOLES This invention relates to a new method of preparing a class of imidazole derivatives which are useful for regulating the natural growth or development of plants.
Compounds which can be prepared using the method of this inventon are 2-imino derivatives of imidazoles and the strong acid salts thereof represented by the formula wherein R is lower alkyl or lower alkoxy lower alkyl, R is lower alkyl, R is lower alkyl or, preferably, hydrogen, R is lower alkyl or, preferably, hydrogen, Z is fluoro, chloro, bromo, lower alkyl, halo lower alkyl or lower alkoxy, n is an integer through 2, m is 0 or 1 and X is the anionic moiety of a strong acid.
As employed herein, the term lower designates those aliphatic radicals of not more than 4 carbon atoms in straight or branched chain. Representative lower alkyl substituents are methyl, ethyl, propyl, isopropyl, butyl, tert. butyl and the like. Where the substituent is alkoxy, it can be methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec. butoxy and the like. When n is 2 the substituents represented by Z can be like or unlike.
The acid salts of the compounds of formula (1) are derived from inorganic and organic acids having a dissociation constant greater than about 5X10- and are, for example, the hydrochloride, hydrobromide, hydroiodide, hydrosulfate, perchlorate, dichloroacetate, trichloroacetate, oxalate, maleate, picrate and the like. Preferred salts are the hydrohalides, such as the hydrochloride and the oxalate.
The method of preparing a class of 2 imino derivatives of substituted imidazole provided by this invention comprises the reaction of a substituted 4- imidazolin-Z-one with phosphorus oxychloride and a primary amine. This method is shown schematically as follows.
N--R Ii 0 HCl c=c if 2 I 13 c" I r.
wherein R, R R R, Z and n are as previously defined.
This new method is economical, providing good yields, and is particularly advantageous on a commercial scale since prior methods of preparing these compounds require the use of alkynylderivatives which are highly unstable and the explosive properties of the alkynyl precursors requires the use of costly safeguards. Thus, the instant invention overcomes this limitation of the methods described in my copending application Ser. No. 329,788, filed Feb. 5, 1973.
The method of preparing the 4-imidazolin-2-one precursors used in this process without the use of derivatives derivaties is described in the joint application of W. D. Dixon and B. R. Dangerfield, entitled Preparation of 4-Imidazolin-2-Ones," filed concurrently herewith. Ser. No. 376,494 filing date July 5, 1973. The description of the preparation of the 4-imidazolin-2-ones in said application, Ser. No. 376,494 is incorporated herein by reference for convenience and not to obscure the instant invention.
In practicing the method of the instant invention the use of phosphorus oxychloride is critical. Although other agents were tried they precluded the formation of the instant 2-imino derivatives upon treatment with the primary amine. Generally, excess phosphorus oxychloride is used in place of solvent. The excess phosphorus oxychloride is usually removed prior to the addition of the primary amine to avoid the use of uneconomical amounts of the amine.
It is necessary to employ elevated temperatures to obtain good yields, for example, about about 40 C up to the reflux temperature of the sytems. Optimum yields are obtained at reflux temperature which is preferred. The pressure employed to carry out the reaction is not critical and can range from subatmospheric to superatmospheric. Usually, the reaction is conducted at normal atmospheric pressure for convenience which provides good yields. Suitable solvents which can be employed in the method of this invention are, for example, haloalkanes, such as, methylene chloride, chloroform, carbontetrachloride and the like.
The 2-imino derivatives of imidazoles prepared by the method of this invention are recovered by employing conventional means, such as, filtration, vacuum stripping, washing and the like. In practicing the method of this invention the compounds of formula 1) wherein X is chloride are directly obtained. These products can be basified with a suitable base, such as, sodium hydroxide to obtain compounds where m is zero, i.e. the free base, which can be readily treated with other strong acids to prepare the desired salt.
The following examples are presented to further illustrate this invention. Parts and percentages are by weight and temperature in degrees centigradeunless otherwise specified.
EXAMPLE 1 Preparation of 1-isopropyl-2-methylimino-3-(3,4-
dichlorophenyl)-4-methyl-4-imidazoline hydrochloride:
To a three neck flask equipped with a stirrer, reflux condenser and addition funnel is charged 5.7g (0.02 mol) of 1-isopropyl-3-(3,4-dichlorophenyl)-4-methyl- 4-imidazolin-2-one in 30 ml of phosphorus oxychloride and heated to reflux. Anhydrous hydrogen chloride gas is slowly bubbled into the solution over a period of about 13 hours. The reaction is cooled and the excess hydrogen chloride and phosphorus oxychloride is removed in vacuuo; The product is dissolved in 50 ml of methylene chloride and excess anhydrous methylamine gas is bubbled into the solution at reflux temperature over a period of about one hour. The reaction is filtered and the filtrate is stripped in vacuuo and crystallized upon scratching to give 5.0g (75% yield) of product. NMR spectral anaylsis confirmed the following structure.
Upon recrystallization chloroform-ethyl acetate, mp 237 -240 C was determined using Mel Temp apparatus.
Anal, Calcd. for C H N C1 C, 50.24; H, 5.42; N, 12.56; Cl, 31.78. Found: C, 50.34; H, 5.42; N, 12.64; Cl, 31.85.
Although hydrogen chloride gas was used in the preparation in Example I it is not required in the practice of this invention as is demonstrated by the following examples.
EXAMPLE II Preparation of 1-isopropyl-2-( 3-methoxypropyl) imino-3-( 3 ,4-dichlorophenyl )-4-methy1-4-imidazoline oxalate:
To a suitable vessel equipped with a stirrer, reflux condenser and addition funnel is charged 5.7g (0.02 mol) of l-isopropyl-3-(3,4-dichlorphenyl)-4-methyl-4- imidazolin-2-one in 30 ml phosphorus oxychloride and heated to reflux temperature with stirring for about 4 hours. Excess phosphorus oxychloride is pulled off under vacuum and 75 ml of methylene chloride is added. With stirring and at reflux temperature 0.2 mol of methoxypropylamine in 30 ml of methylene chloride is added dropwise over a period of about twenty minutes. After an additional 45 minutes the solvent is removed in vacuuo. The hydrochloride product obtained is dissolved in 50 ml of water and extracted twice with 25 ml portions of diethyl ether. The aqueous layer is cooled over ice and approximately 50 ml of sodium hydroxide is added. The free base is purified by extracting with diethyl ether (3X50 ml) washing with water (2X30 ml) drying over anhydrous magnesium sulfate and placing under high vacuum for 10 minutes.
The free base (6.18g) is then dissolved in 5 ml acetone, cooled and one equivalent of oxalic acid dihydrate in 10 ml of acetone is added. About 50 ml of ethyl acetate is added and the product crystallizes. The mixture is cooled filtered and dried to give 6.3g (71% yield) of product having the following structure which is confirmed by NMR spectral analysis.
if- (CH 00H on c H-C-N N 01 H c o cn 2 4 c c l l H on EXAMPLE III Preparation of l-isopropyl-2-(3-methoxypropyl) imino-3-phenyl-4-imidazoline oxalate:
To a suitable vessel equipped with a stirrer, reflux condenser and addition funnel is charged 206.5 g (0.95 mol) of 1-isopropyl-3-phenyl-4-methyl-4-imidazolin- 2-one in 1100 ml of phosphorus oxychloride and is heated to reflux with stirring for about 5 hours. Excess phosphorus oxychloride is removed under high vacuum. About 1000 ml of methylene chloride is added and heated to reflux and 890 g of methoxypropylamine is slowly added over a period of 1.5 hours and held at reflux with stirring for 3 hours. The reaction is cooled and the solvent is removed in vacuuo. The hydrochloride salt is dissolved in 1000 ml water and extracted with 3 250 ml of diethyl ether. The aqueous layer is made basic by the addition of 1500 g of cold 25% sodium hydroxide solution and then extracted with 5X200 ml of diethyl ether, dried over magnesium sulfate and subjected to high vacuum to remove any residual methoxypropyl amine. Approximately 204.7g of the free base is obtained which is dissolved in 200 ml of acetone and a solution of 94 g of oxalic acid dihydrate in about 300 ml of acetone is added. The solution is diluted with an equal volume of ethyl acetate and cooled to provide 181 g. of product. The mother liquor is evaporated and the residue recrystallized from isopropanol to give an additional 11.6 g of product for total yield of 192.6 g NMR spectral analysis of the product confirmed the following structure.
N- (CH OCHS EXAMPLE IV Preparation of l-methyl-2-(3-methoxypropy)imino- 3-(3,4-dichlorophenyl)-4-methyl-4-imidazoline oxalate.
To a suitable vessel equipped with a stirrer, reflux condenser and addition funnel is charged about 25.7 g (0.1 mol)' of l-methyl-3-(3,4-dichlorophenyl)-4- methyl-4-imidazolin-2-one in 125 ml of phosphorus oxychloride and heated to reflux temperature with stirring for a period of about hours. The reaction is cooled and excess phosphorus oxychloride is removed under vacuum and 300 ml of methylene chloride is added and heated to reflux while slowly adding 89.14 (1.0 mol) of 3-methoxypropylamine with stirring and maintained at reflux for about 2 hours. The reaction is cooled and the solvent is removed in vacuuo. The resulting hydrochloride product is dissolved in 250 ml of water and extracted with 2 l25 ml of ether. The aqueous layer is cooled and about 160 g of aqueous sodium hydroxide is added. The solution is extracted with 3Xl50 ml of diethyl ether, dried over magnesium sulfate filtered and the solvent is removed under vacuum. The free base obtained 22.7 g is dissolved in 50 ml of acetone and 8.7 g oxalic acid dihydrate in 60 ml of acetone is added which provides 26.7 g of product. NMR spectral analysis of the product, mp l5l-l54, confirms the following structure.
lI :-(CH OCH ou -1:1 1|r- 1 H2 c 0 C: C l H CH Using the procedure set forth in Example IV but replacing the 4-imidazolin-2-one with other appropriate imidazolin-2-ones or replacing the amine with other appropriate amines the following compounds are prepared.
V l-Isopropyl-2-n-butylimino-3-( 3 ,4-
dichlorophenyl)-4-methyl-4-imidazoline oxalate, mp l5816l VI. l-Propyl-2-( 3-methoxypropyl)imino-3-( 3 ,4- dichlorophenyl)-4-methyl-4-imidazoline oxalate, mp ll6-l 19 VII. l-Butyl-2-(3-methoxypropyl)imino-3-(3,4- dichlorophenyl)-4-methyl-4-imidazoline oxalate, mp ll8-122 VIII. l-Methyl-2-(3-methoxypropyl)imino-3-phenyl- 4-methyl-4-imidazoline oxalate, mp 131 -l33 IX l-Isopropyl-2-( 3-methoxypropyl)imino-3-( 3- trifluoromethylphenyl)-4-methyl-4-imidazoline oxalate, mp 9599 X. l-Methyl-2-(3-isopropoxypropyl)imino-3 phenyl-4-methyl-4-imidazoline oxalate, mp l33l35 The compounds of formula (1) prepared in accordance with the method of this invention are effective for regulating the natural growth or development of plants. The compounds of the foregoing examples when applied to representative plants, such as soybeans, at various stages of growth, elicit a growth regulation response. The treated plants develop a darker green foliar color and develop into more effective plants. Further details of the beneficial properties of the compounds are found in pending application Ser.
,- 6 No. 329,787, filed Feb. 5, 1973, by W. D. Dixon and G. L. Eilrich.
Although this inventionihas been described with respect to specific modification, the details thereof are not to be construed as limitations, for it will be apparent that various equivalents, changes and modifications may be resorted to without departing from the spirit and scope thereof and it is understood that such equivalent embodiments are intende d to be included herein.
The embodiments of the inventiori in which an exclusive property "or privilege is claimed are defined as follows:
1. A process for preparing a compound of the formula wherein: R is lower alkyl or lower alkoxy lower alkyl, R is lower alkyl; R is lower alkyl or hydrogen; R is lower alkyl or hydrogen; Z is fluoro, chloro, bromo, lower alkyl, halo lower alkyl, or lower alkoxy and n is an integer zero through 2, which comprises reacting at temperatures from about 40C. up to the reflux temperature of the system a 4-imidazolin-2-one of the formula wherein R, R R", Z and n are as defined above, with phosphorus oxychloride and a primary amine of the formula H NR wherein R is as defined above.
2. The process of claim 1 which comprises as a first step the reaction-of the 4-imidazolin-2-one in an excess of phosphorus oxychloride at reflux temperature and as a second step the removal of excess phosphorus oxychloride and reacting the product with an excess of the primary amine in an inert solvent at an elevated temperature.
3. The process of claim 2 wherein the elevated temperature is the reflux temperature of the system.
4. The process of claim 2 wherein the solvent is methylene chloride.
5. The process of claim 2 wherein the 4-imidazolin- 2-one is of the formula wherein R is lower alkyl; Z is fluoro, chloro, bromo, lower alkyl, halo lower alkyl, or lower alkoxy; and n is an integer zero through 2. i
6. The process of claim'S wherein the 4-imidazolin- 2-one is 1-isopropyl-3-(3,4-dichlor0phenyl)-4-methyl- 4-imidazolin-2-one.
7'. The process of claim 5 wherein the primary amine is methoxypropylamine.
" '8. The process of claim 6 wherein the primary amine imidazolin-2-one.
Claims (11)
1. A PROCESS FOR PREPARING A COMPOUND OF THE FORMULA
1. A process for preparing a compound of the formula
2. The process of claim 1 which comprises as a first step the reaction of the 4-imidazolin-2-one in an excess of phosphorus oxychloride at reflux temperature and as a second step the removal of excess phosphorus oxychloride and reacting the product with an excess of the primary amine in an inert solvent at an elevated temperature.
3. The process of claim 2 wherein the elevated temperature is the reflux temperature of the system.
4. The process of claim 2 wherein the solvent is methylene chloride.
5. The process of claim 2 wherein the 4-imidazolin-2-one is of the formula
6. The process of claim 5 wherein the 4-imidazolin-2-one is 1-isopropyl-3-(3,4-dichlorophenyl)-4-methyl-4-imidazolin-2-one.
7. The process of claim 5 wherein the primary amine is methoxypropylamine.
8. The process of claim 6 wherein the primary amine is methylamine.
9. The process of claim 6 wherein the primary amine is methoxypropyl amine.
10. The process of claim 7 wherein the 4-imidazolin-2-one is 1-isopropyl-3-phenyl-4-methyl-imidazolin-2-one.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US376493A US3887577A (en) | 1973-07-05 | 1973-07-05 | Process for the preparation of 2-imino derivatives of substituted imidazoles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US376493A US3887577A (en) | 1973-07-05 | 1973-07-05 | Process for the preparation of 2-imino derivatives of substituted imidazoles |
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| Publication Number | Publication Date |
|---|---|
| US3887577A true US3887577A (en) | 1975-06-03 |
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| Application Number | Title | Priority Date | Filing Date |
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| US376493A Expired - Lifetime US3887577A (en) | 1973-07-05 | 1973-07-05 | Process for the preparation of 2-imino derivatives of substituted imidazoles |
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| Country | Link |
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| US (1) | US3887577A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4459411A (en) * | 1982-09-13 | 1984-07-10 | The Dow Chemical Company | Preparation of unsaturated heterocyclic carbonyl-containing compounds |
| EP1391456A1 (en) * | 2001-04-19 | 2004-02-25 | Eisai Co., Ltd. | 2-iminoimidazole derivative (2) |
| US20060058370A1 (en) * | 2003-02-19 | 2006-03-16 | Eisai Co., Ltd. | Methods for producing cyclic benzamidine derivatives |
-
1973
- 1973-07-05 US US376493A patent/US3887577A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| Burmistrov et al., C. A., Vol. 62: 14657, (1965). * |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4459411A (en) * | 1982-09-13 | 1984-07-10 | The Dow Chemical Company | Preparation of unsaturated heterocyclic carbonyl-containing compounds |
| EP1391456A4 (en) * | 2001-04-19 | 2006-02-01 | Eisai Co Ltd | 2-iminoimidazole derivative (2) |
| US20040242627A1 (en) * | 2001-04-19 | 2004-12-02 | Shuichi Suzuki | 2-Iminoimidazole derivatives (1) |
| US20050004204A1 (en) * | 2001-04-19 | 2005-01-06 | Shuichi Suzuki | 2-Iminopyrrolidine derivatives |
| US20050004197A1 (en) * | 2001-04-19 | 2005-01-06 | Shichi Suzuki | 2-iminoimidazole derivatives (2) |
| US20050245592A1 (en) * | 2001-04-19 | 2005-11-03 | Shuichi Suzuki | 2-Iminopyrrolidine derivatives |
| EP1391456A1 (en) * | 2001-04-19 | 2004-02-25 | Eisai Co., Ltd. | 2-iminoimidazole derivative (2) |
| US7244730B2 (en) | 2001-04-19 | 2007-07-17 | Eisai Co., Ltd | 2-iminopyrrolidine derivatives |
| US7304083B2 (en) | 2001-04-19 | 2007-12-04 | Eisai R&D Management Co., Ltd. | 2-iminoimidazole derivatives (2) |
| US7476688B2 (en) | 2001-04-19 | 2009-01-13 | Eisai R&D Management Co., Ltd. | Cyclic amidine derivatives |
| US20090215795A1 (en) * | 2001-04-19 | 2009-08-27 | Eisai R&D Management Co., Ltd. | Cyclic amidine derivatives |
| US20060058370A1 (en) * | 2003-02-19 | 2006-03-16 | Eisai Co., Ltd. | Methods for producing cyclic benzamidine derivatives |
| US7375236B2 (en) | 2003-02-19 | 2008-05-20 | Eisai Co., Ltd. | Methods for producing cyclic benzamidine derivatives |
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